The behavior of malignant cells is widely accepted to be associated with alterations in the plasma membrane of these cells following transformation. It has been recently established by the Principal Investigator that a surface protein present on normal fibroblasts but missing from transformed cells plays a functional role in the adhesion of cells to collagen-coated surfaces. In accordance with this biological activity the protein has been designated cell adhesion factor (CAF). We propose to more fully investigate the mechanism involved in CAF mediated adhesion on a molecular level. These experiments will involve a study of the chemical association between collagen and CAF, and the involvement of protein synthesis, energy requirements, and the role of the cell structures in adhesion. In addition, as an approach to identifying regions of CAF involved in biological functioning, cyanogen bromide fragments of the protein will be generated, isolated and assayed for biological activity. Comparison of the structural features of intact plasma membrane CAF and CAF shed into the medium should provide insight into the process of CAF loss from normal cell surfaces. Hopefully, this type of analysis will provide a direction for further investigation of the abnormal process of loss from transformed cells. As an extension of the role of CAF in attachment, we plan to study the effect of exogenous and endogenous CAF on cell migration and invasiveness in in vitro model systems. Finally, plasma levels of CAF will be determined by radioimmunassay and correlated with disease states in patients with a variety of malignant and benign diseases.